气候变化领域集成服务门户(CCPortal): Mitochondrial metabolism is essential for invariant natural killer T cell development and function

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DOI	10.1073/pnas.2021385118
	Mitochondrial metabolism is essential for invariant natural killer T cell development and function
	Weng X.; Kumar A.; Cao L.; He Y.; Morgun E.; Visvabharathy L.; Zhao J.; Sena L.A.; Weinberg S.E.; Chandel N.S.; Wang C.-R.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Conventional T cell fate and function are determined by coordination between cellular signaling and mitochondrial metabolism. Invariant natural killer T (iNKT) cells are an important subset of “innate-like” T cells that exist in a preactivated effector state, and their dependence on mitochondrial metabolism has not been previously defined genetically or in vivo. Here, we show that mature iNKT cells have reduced mitochondrial respiratory reserve and iNKT cell development was highly sensitive to perturbation of mitochondrial function. Mice with T cell-specific ablation of Rieske iron-sulfur protein (RISP; T-Uqcrfs1−/−), an essential subunit of mitochondrial complex III, had a dramatic reduction of iNKT cells in the thymus and periphery, but no significant perturbation on the development of conventional T cells. The impaired development observed in T-Uqcrfs1−/− mice stems from a cell-autonomous defect in iNKT cells, resulting in a differentiation block at the early stages of iNKT cell development. Residual iNKT cells in T-Uqcrfs1−/− mice displayed increased apoptosis but retained the ability to proliferate in vivo, suggesting that their bioenergetic and biosynthetic demands were not compromised. However, they exhibited reduced expression of activation markers, decreased T cell receptor (TCR) signaling and impaired responses to TCR and interleukin-15 stimulation. Furthermore, knocking down RISP in mature iNKT cells diminished their cytokine production, correlating with reduced NFATc2 activity. Collectively, our data provide evidence for a critical role of mitochondrial metabolism in iNKT cell development and activation outside of its traditional role in supporting cellular bioenergetic demands. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CD1; Knockout mice; Mitochondrial metabolism; NKT cells; T cell development
语种	英语
scopus关键词	interleukin 15; iron sulfur protein; T lymphocyte receptor; ubiquinol cytochrome c reductase; animal cell; animal experiment; animal model; apoptosis; Article; bioenergy; biosynthesis; cell damage; cell differentiation; cell function; cell maturation; cell proliferation; controlled study; cytokine production; disorders of mitochondrial functions; gene activity; in vivo study; knockout mouse; mitochondrial respiration; mouse; natural killer T cell; NFATc2 gene; nonhuman; priority journal; protein expression; reduction (chemistry); signal transduction; T-Uqcrfs1 gene
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180081
作者单位	Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
推荐引用方式 GB/T 7714	Weng X.,Kumar A.,Cao L.,et al. Mitochondrial metabolism is essential for invariant natural killer T cell development and function[J],2021,118(13).
APA	Weng X..,Kumar A..,Cao L..,He Y..,Morgun E..,...&Wang C.-R..(2021).Mitochondrial metabolism is essential for invariant natural killer T cell development and function.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Weng X.,et al."Mitochondrial metabolism is essential for invariant natural killer T cell development and function".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).